The Complex Role of Microglia in Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), leading to severe physical and cognitive impairments. Recent studies have highlighted the pivotal role of microglia—CNS-resident immune cells—in the progression and potential treatment of MS. This blog post delves into the latest research focusing on microglia-specific gene variations and their implications in MS, drawing insights from key papers published in the last few years.
Microglial Diversity and Gene Variations in MS
Microglia exhibit diverse phenotypes which can have both neuroprotective and neurodestructive outcomes in MS. A study by Zia et al. (2020) explores the broad functional roles of microglia from their origins to their heterogeneity across different conditions, emphasizing their dual roles in neurotoxicity and regeneration in MS (Zia et al., 2020).
Gene Expression Changes Over Disease Progression
Further research by Vainchtein et al. (2022) on a mouse model of secondary progressive MS reveals how microglial gene expression varies dramatically across different disease phases. This study shows that microglia shift from a pro-inflammatory phenotype during acute phases to a more regenerative state during remission, providing a detailed temporal map of microglial activities in progressive MS (Vainchtein et al., 2022).
Microglia and the Mertk Gene
Shen et al. (2021) focus on the 'Mertk' gene, associated with MS risk, which is crucial for microglial activation and effective remyelination. The study details how Mertk-deficient mice show compromised phagocytosis and remyelination, indicating a potential therapeutic target for enhancing microglial function in MS (Shen et al., 2021).
Conclusion
Recent research into microglia-specific gene variations has vastly improved our understanding of their dual roles in MS, identifying potential targets for therapeutic intervention. The studies reviewed here underscore the importance of genetic factors in microglial behavior and offer promising pathways for developing more effective MS treatments.
Reference:
Zia, S., Rawji, K., Michaels, N., Burr, M., Kerr, B., Healy, L., & Plemel, J. (2020). Microglia Diversity in Health and Multiple Sclerosis. Frontiers in Immunology, 11.
Vainchtein, I., Alsema, A., Dubbelaar, M., Grit, C., Vinet, J., Weering, H., Al‐Izki, S., Biagini, G., Brouwer, N., Amor, S., Baker, D., Eggen, B., Boddeke, E., & Kooistra, S. (2022). Characterizing microglial gene expression in a model of secondary progressive multiple sclerosis. Glia, 71, 588 - 601.
Shen, K., Reichelt, M., Kyauk, R., Ngu, H., Shen, Y., Foreman, O., Modrušan, Z., Friedman, B., Sheng, M., & Yuen, T. (2021). Multiple sclerosis risk gene Mertk is required for microglial activation and subsequent remyelination.. Cell reports, 34 10, 108835 .
